The Surgery Branch Vector Production Facility (SBVPF) was established to provide clinical-grade retroviral and lentiviral vectors to support of our gene therapy clinical trials with the goal of providing GMP quality products while reducing production time and cost. These products, both retroviral and lentiviral vectors will be used to introduce novel T cell receptors (TCR) or chimeric antigen receptors (CAR) to genetically modify naive T cells to make them specifically recognize and kill tumor. This lab provides all the clinical reagents for our clinical gene therapy program. For this report, SBVPF recently manufactured a several TCRs targeting KRAS hotspot mutations at position 12. In addition, our focus is now to isolate T cell receptors targeting nonsynonymous mutations presented by tumors from tumor infiltrating lymphocytes residing within the given tumor. Our laboratory has also provided cloning services to our group. We have constructed lentiviral vectors using gateway technology for cell reprogramming. We have also developed new clinical retroviral and lentiviral vector backbones to facilitate our clinical reagent program. We are also generating adenoviral vector constructs. My lab also developed a novel closed cell production process for specifically for our CD19 CAR clinical efforts. This new production process allows for generation of a clinical CD19 CAR cell product in 6 days and the final cell product is cryopreserved to allow flexibility in scheduling the patient's treatment. Lastly, we are testing a new hypothesis that immunogenic mutations (neoantigens) presented on a patient's tumor mediate tumor regression by TIL. In some cases, TIL cannot be generated, but TCRs can be cloned. In these instances we can use a gene therapy approach to treat patients by introducing neoantigen-specific TCRs into autologous PBMC, expanding the transduced cells ex vivo and administering to the patient. We have developed two transient vector production platforms, gammaretroviral and lentiviral, that support GMP-compliant transient vector production single patient treatments targeting neoantigens.